Epithelium-Penetrable Nanoplatform with Enhanced Antibiotic Internalization for Management of Bacterial Keratitis

作者:Zhang, YL (Zhang, Yanlong)^{[ 1,2,3,4 ]} ; Yu, YJ (Yu, Yunjian)^{[ 5 ]} ; Li, G (Li, Gang)^{[ 1,2 ]} ; Zhang, XG (Zhang, Xinge)^{[ 5 ]} ; Wu, ZM (Wu, Zhongming)^{[ 6,7 ]} ; Lin, L (Lin, Ling)^{[ 1,2 ]}

BIOMACROMOLECULES, 2021, 22(5): 2020-2032

DOI: 10.1021/acs.biomac.1c00139

摘要

A standardized regimen for addressing the adverse effects of bacterial keratitis on vision remains an intractable challenge due to poor epithelial penetration and a short corneal retention time. In this study, a new strategy is proposed to implement the direct transport of antibiotics to bacteria-infected corneas via topical administration of an epithelium-penetrable biodriven nanoplatform, thereby enabling the efficacious treatment of bacterial keratitis. The nanoplatforms were composed of amphiphilic glycopolymers containing boron dipyrromethene and boronic acid moieties with stable fluorescence characteristics and the ability to potentiate epithelial penetration deep into the cornea. The boronic acid-derived nanoplatforms enabled efficient cellular internalization through the high affinity of boric acid groups for the diol-containing bacterial cell wall, resulting in enhanced drug penetration and retention inside the pathogenic bacteria. The bacterial cells formed agglomerations after incorporating the nanoplatforms along with a special mechanism to release the encapsulated cargo in response to in situ bacteria. Compared with the drug alone, this smart system achieved enhanced bacterial mortality and attenuated inflammation associated with Staphylococcus aureus-induced keratitis in rats, demonstrating a paradigm for targeted ocular drug delivery and an alternative strategy for managing bacterial keratitis or other bacterial infections by heightening corneal permeability and transcorneal bioavailability.